May 14, 2014

New Cellular Study Indicates Schizophrenia Begins In The Womb

New research from a large team of American researchers has revealed evidence that schizophrenia may originate during fetal development in the womb.

For the study, published in the journal Molecular Psychiatry, researchers analyzed neurons grown in the laboratory from the skin cells of individuals with schizophrenia. The study team noted in its report that these neurons behaved strangely and a similar type of neuronal development in the womb could be a root cause for schizophrenia.

"This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia," said study author Fred H. Gage, a professor of genetics at the Salk Institute for Biological Studies in La Jolla, California. "We were surprised at how early in the developmental process that defects in neural function could be detected."

Scientists currently do not know much regarding the underlying causes of schizophrenia, including which cells in the brain are affected and how. Previous research only had the opportunity to analyze schizophrenia by evaluating the brains of individuals with the condition after death. The effects of age, stress, treatment or substance abuse often ruined the minds of these individuals – making it challenging to pinpoint the disease's beginnings.

To skirt around these confounding effects, the study team took skin cells from people with schizophrenia, engineered the cells into a stem cell form, and then pushed them to become extremely early-stage neurons called neural progenitor cells (NPCs). These NPCs are very similar to the cells found in the brain of a developing fetus.

"We realized they weren't mature neurons but only as old as neurons in the first trimester," said study author Kristen Brennand, the first author of the paper and assistant professor at Icahn School of Medicine at Mount Sinai. "So we weren't studying schizophrenia but the things that go wrong a long time before patients actually get sick."

The scientists produced NPCs from the skin cells of four patients with schizophrenia and six individuals without the condition. They screened the cells in two kinds of assays: one in which they viewed how far the cells moved and acted on selected surfaces – and one in which they measured stress in the cells by imaging mitochondria, which are small energy-generating organelles.

The results on both tests showed major discrepancies between cells taken from those with schizophrenia and those without the condition. Cells linked to schizophrenia exhibited abnormal activity in two main classes of proteins: those related to adhesion and connectivity, and those related to oxidative stress. The cells from individuals with schizophrenia also seemed to have both unusual migration – which may cause the development of poor connectivity – and heightened levels of oxidative stress.

The study team said their findings are in keeping with a predominant theory that states events happening during pregnancy can give rise to schizophrenia, despite the fact that the disease doesn't reveal itself until early adulthood. Past analyses indicate that mothers who suffer from an infection, poor nutrition or extreme stress during pregnancy are at a greater risk of having children who will develop schizophrenia. Scientists suspect both genetic and environmental factors likely play a role in the development of the condition.

"The study hints that there may be opportunities to create diagnostic tests for schizophrenia at an early stage," Gage said.